Regeneration of injured nerve fibers into the central nervous system will be studied in rat at various ages using the central process of dorsal root ganglion (DRG) as a model system. Factors controlling the success or failure of dorsal root regeneration will be examined with emphasis on the transitional zone between the peripheral (PNS) and central nervous system (CNS) and the induction of Schwann cells during the regenerative process. The role of nerve growth factor (NGF) obtained from central and peripheral sources in maintaining the homeostasis of DRG sensory neuron will be defined. The work will clarify the function of NGF in the response of the sensory neuron to axonal injury in terms of neuronal cell body reaction and regenerative capability. The pharmacological potential of NGF to enhance regeneration of dorsal root into the CNS and to improve functional recovery will be assessed. The results of the experiments proposed in this study will provide the first system in the CNS in which a putative trophic factor is defined, which in turn contribute to understanding the relative effects of trophic factors in the CNS and PNS. Regeneration of crushed dorsal root into the CNS will be evaluated by: 1) physiological (axonal transport of radiolabelled proteins or HRP and pinch test); 2) histological (neuronal and axonal counts and morphological analysis); 3) biochemical (levels of neuropeptides and extralysosomal acid phosphatases) techniques. The ability of a pharmacological dose of NGF to enhance dorsal root regeneration after injury will be evaluated with similar methods. NGF will be tested as a neurotrophic or neurite-promoting agent by systemic administration or local application at the denervated spinal cord. Finally, the role of CNS target tissues and of endogenous NGF as a possible target- derived substance in the trophic support of DRG neurons will be studied.